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?Anadir un anestesico al spray bucal de nicotina aumentaria las tasas de abstinencia tabaquica? ?Se justifica por ello iniciar un proyecto de investigacion?

Sr. Director: Aunque las propiedades adictivas del tabaco dependen de la nicotina, ese poder adictivo refleja complicadas interacciones entre la droga y el contexto en el que esta es liberada. Es conocido que existen componentes sensoriales que contribuyen a la satisfaccion experimentada por el fumador, existiendo una senal sensorial asociada a la droga que se convierte en un reforzador condicionado asociado al tabaco. Senales asociadas con cada calada de humo de tabaco, como por ejemplo estimulos visuales, olfatorios o gustativos, provocan estados subjetivos que pueden disparar la conducta de busqueda de la droga y favorecer asi la recaida en el consumo (Dani y Balfour, 2011). Recientemente, Liu (2014) ha demostrado el papel de la neurotransmision colinergica, a traves de la activacion del receptor alfa7 de acetilcolina en la mediacion en las propiedades reforzadoras de la nicotina debidas a senales externas, por lo que manipular la actividad del receptor alfa7 de acetilcolina podria ser una diana en el desarrollo de farmacos que prevengan las recaidas motivadas por senales ambientales.

Hasta que la investigacion neurocientifica aclare el tema, hay que decir que cuando el humo del cigarrillo llega a la boca del fumador y pasa a la faringe, laringe y al tracto respiratorio inferior se producen una variedad de sensaciones, habiendose hipotetizado que estas senales quimio-sensoriales se convierten en potentes estimulos de refuerzo condicionado debido a su asociacion con el efecto reforzador de la nicotina en el sistema nervioso central (Smolka, et al., 2006). Es mas, incluso se ha comprobado como los factores sensoriales podrian ser tan importantes en la satisfaccion tras fumar, aceptacion del producto y en el deseo de fumar como los factores farmacologicos de la nicotina a nivel cerebral (Pritchard, Robinson, Guy, Davis y Stiles, 1996). Rose, Zinser, Tashkin, Newcomb y Ertle (1984) demostraron como anestesiar el tracto respiratorio superior e inferior reducia el craving por la nicotina y el numero de caladas deseadas. La satisfaccion experimentada por fumadores que inhalan tabaco disminuye si las vias aereas superiores e inferiores son anestesiadas (Rose, Tashkin, Ertle, Zinser y Lafer, 1985). Hasta donde nosotros conocemos esta linea de investigacion no fue continuada posteriormente.

Actualmente disponemos del spray bucal de nicotina para ayudar a dejar de fumar que ha probado su eficacia para aumentar las posibilidades de un fumador de mantenerse abstinente (T0nnesen, Lauri, Perfekt, Mann, y Batra, 2012). Existe evidencia de que las formulaciones de terapia sustitutiva con nicotina de liberacion rapida actuan aliviando rapidamente el craving consiguiendo asi calmar el discomfort por la abstinencia (Hansson, Hajek, Perfekt y Kraiczi, 2012). Reducir la tentacion de fumar, aliviando el craving, disminuira las caidas en el consumo. El spray bucal de nicotina ha demostrado un rapido alivio del craving (Hansson, et al., 2012).

Aunque, que sepamos, no existen trabajos que hayan valorado la abstinencia tabaquica tras anadir un anestesico a la terapia sustitutiva con nicotina habitualmente empleada, la pregunta en este punto seria; ?anadir un anestesico al spray bucal de nicotina lograria unas mayores tasas de abstinencia tabaquica? Con ello sumariamos dos efectos a la vez para mantener la abstinencia; por un lado la rapida absorcion de la nicotina demostrada por el spray bucal (Hansson et al., 2012) que alivia de forma rapida el craving y, por otro, el anestesico disminuiria igualmente el craving y la satisfaccion que experimenta el fumador que inhala tabaco mitigando asi los efectos sensoriales de la nicotina y por lo tanto disminuyendo el estimulo de refuerzo condicionado que esta provoca, logicamente la clave es la duracion del efecto anestesico. Aunque no tenemos contestacion a lo anterior, quiza lo expuesto en esta carta justificaria el desarrollo de un proyecto de investigacion que le pudiera dar respuesta.

Enviar correspondencia a: Dr. Jose Ignacio de Granda-Orive. C/ Cavanilles 43, 7 E, Madrid 28007. E-mail: igo01m@gmail.com

Referencias

Dani, J. A. y Balfour, D. J. K. (2011). Historical and current perspective on tobacco use and nicotine addiction. Trends in Neuroscience, 34, 383-392. doi: 10.1016/j.tins.2011.05.001

Hansson, A., Hajek, P., Perfekt, R., y Kraiczi, H. (2012). Effects of nicotine mouth spray on urges to smoke, a randomised clinical trial. BMJ Open, 2, pii: e001618. doi: 10.1136/bmjopen-2012-001618.

Liu, X. (2014). Effects of blockade of a4p2 and a7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats. International Journal of Neuropsychopharmacology, 17, 105-116. doi: 10.1017/S1461145713000874

Pritchard, W. S., Robinson, J. H., Guy, T. D., Davis, R. A., y Stiles, M. F. (1996). Assessing the sensory role of nicotine cigarette smoking. Phychopharmacology(Berl), 127, 55-62.

Rose J. E., Tashkin, D. P, Ertle, A., Zinser, M. C., y Lafer, R. (1985). Sensory blockade of smoking satisfaction. Pharmacology Biochemistry and Behavior, 23, 289-293.

Rose, J. E., Zinser, M. D., Tashkin, D. P, Newcomb, R., y Ertle, A. (1984). Subjetive response to cigarette smoking following airway anesthetization. Addictive Behaviors, 9, 211-215.

Smolka, M. N., Buhler, M., Klein, S., Zimmermann, U., Mann, K., Heinz, A., ... Braus, D. F. (2006). Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery. Psychopharmacology (Berl), 184, 577-588.

Tonnesen, P, Lauri, H., Perfekt, R., Mann, K., y Batra, A. (2012). Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial. European Respiratory Journal, 40, 548-554. doi:10.1183/09031936.00155811.

JOSE IGNACIO DE GRANDA-ORIVE, SEGISMUNDO SOLANO-REINA *, CARLOS A. JIMENEZ-RUIZ **

Servicio de Neumologia, Hospital Universitario 12 de Octubre, Madrid. * Servicio de Neumologia, Hospital Universitario Gregorio Maranon, Madrid. ** Unidad Especializada en Tabaquismo de la Comunidad de Madrid, Madrid.

Would Adding an Anesthesic to Nicotine Mouth Spray Increase Smoking Cessation Rates? Would this Justify Starting a Research Project?

Dear Sir: Although the addictive properties of tobacco depend on nicotine, this addictive power reflects complex interactions between the drug and the context in which it is released. It is known that there are sensory components that contribute towards the satisfaction felt by the smoker, there being a sensory cue associated with the drug that makes it a conditioned replenisher associated with tobacco. There are nicotine-associated cues with each puff such as, for example, visual, olfactory and gustatory stimuli, that provoke subjective states that can in turn trigger off the search for the drug and thus lead to relapse (Dani and Balfour, 2011). Recently, Liu (2014) has shown the role of cholinergic neurotransmission, via the activation of the acetylcholine receptor alpha7, in the mediation of the conditioned incentive properties of external nicotine cues, for which reason manipulating the activity of the acetylcholine receptor alpha7 could be a target in the development of drugs to prevent relapse brought on by outward cues.

Until such time as neuroscientific research clears up the matter, it has to be said that when cigarette smoke enters the smoker's mouth and passes the pharynx, the larynx and the lower respiratory tract a series of sensations are provoked, it having been hypothesized that these chemosensory signals become powerful conditioned reinforcement stimuli owing to their being associated with the replenishing effect of the nicotine on the central nervous system (Smolka et al., 2006). Indeed, it has even been shown that sensory factors may be as important in the sensation of satisfaction after smoking, the acceptance of the product and on the desire to smoke as the pharmacological factors of nicotine on a cerebral level (Pritchard, Robinson, Guy, Davis y Stiles, 1996). Rose, Zinser, Tashkin, Newcomb y Ertle (1984) showed that anesthetizing the upper and lower respiratory tracts reduced the craving for nicotine and the number of puffs desired. The satisfaction experienced by smokers who inhale diminishes if the upper and lower areas are anesthetized (Rose, Tashkin, Ertle, Zinser y Lafer, 1985). As far as we know, this line of research was not continued afterwards.

We currently have available the nicotine mouth spray to help smokers stop and it has shown its efficacy in increasing the smoker's chances of remaining abstinent (T0nnesen, Lauri, Perfekt, Mann, and Batra, 2012). There is evidence that fast-acting nicotine replacement therapy prescriptions work quickly to alleviate craving and thus calm the discomfort caused by abstinence (Hansson, Hajek, Perfekt and Kraiczi, 2012). Reducing the temptation to smoke, by alleviating the craving, will diminish the number of relapses. Nicotine mouth spray has shown that it alleviates craving rapidly (Hansson et al., 2012).

However, as far as we know, there are no studies that have measured smoking abstinence after adding an anesthetic to the nicotine replacement therapy habitually employed and the question at this point would be: would adding an anesthetic to nicotine mouth spray increase smoking abstinence rates? With this we would add two effects at the same time as maintaining abstinence; on the one hand the proven rapid absorption of nicotine via the mouth spray (Hansson et al., 2012) which quickly alleviates craving and, on the other, the anesthetic would equally diminish the craving and the satisfaction that the smoker experiences when inhaling tobacco smoke thus lessening the sensory effects of the nicotine and, therefore, diminishing the conditioned reinforcement stimulus that it leads to. Logically, the key is in the duration of the anesthetic effect. Although we have no answer to the above, possibly what we have expounded in this letter would justify a research project to find such a response.

Send correspondence to:

Dr. Jose Ignacio de Granda-Orive. C/ Cavanilles 43, 7 E, Madrid 28007. E-mail: igo01m@gmail.com

References

Dani, J. A. & Balfour, D. J. K. (2011). Historical and current perspective on tobacco use and nicotine addiction. Trends in Neuroscience, 34, 383-392. doi: 10.1016/j. tins.2011.05.001

Hansson, A., Hajek, P., Perfekt, R., & Kraiczi, H. (2012). Effects of nicotine mouth spray on urges to smoke, a randomised clinical trial. BMJ Open, 2, pii: e001618. doi: 10.1136/bmjopen-2012-001618.

Liu, X. (2014). Effects of blockade of [alpha]4[beta]2 and [alpha]7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats. International Journal of Neuropsychopharmacology, 17, 105-116. doi: 10.1017/S1461145713000874

Pritchard, W. S., Robinson, J. H., Guy, T. D., Davis, R. A., & Stiles, M. F. (1996). Assessing the sensory role of nicotine cigarette smoking. Phychopharmacology(Berl), 127, 55-62.

Rose J. E., Tashkin, D. P, Ertle, A., Zinser, M. C., & Lafer, R. (1985). Sensory blockade of smoking satisfaction. Pharmacology Biochemistry and Behavior, 23, 289-293.

Rose, J. E., Zinser, M. D., Tashkin, D. P, Newcomb, R., & Ertle, A. (1984). Subjetive response to cigarette smoking following airway anesthetization. Addictive Behaviors, 9, 211-215.

Smolka, M. N., Buhler, M., Klein, S., Zimmermann, U., Mann, K., Heinz, A., ... Braus, D. F. (2006). Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery. Psychopharmacology (Berl), 184, 577-588.

Tonnesen, P, Lauri, H., Perfekt, R., Mann, K., & Batra, A. (2012). Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial. European Respiratory Journal, 40, 548-554. doi: 10.1183/09031936.00155811.

JOSE IGNACIO DE GRANDA-ORIVE, SEGISMUNDO SOLANO-REINA *, CARLOS A. JIMENEZ-RUIZ **

Servicio de Neumologia, Hospital Universitario 12 de Octubre, Madrid. * Servicio de Neumologia, Hospital Universitario Gregorio Maranon, Madrid. ** Unidad Especializada en Tabaquismo de la Comunidad de Madrid, Madrid.
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Title Annotation:cartas al director
Author:de Granda-Orive, Jose Ignacio; Solano-Reina, Segismundo; Jimenez-Ruiz, Carlos A.
Publication:Adicciones
Article Type:Carta al editor
Date:Jun 1, 2015
Words:1903
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